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Although the concept that the blood-brain barrier (BBB) plays an important role in the etiology and pathogenesis of Alzheimer's disease (AD) has become increasingly accepted, little is known yet about how it actually contributes. We and others have recently identified a novel functionally distinct subset of BBB pericytes (PCs). In the present study, we sought to determine whether these PC subsets differentially contribute to AD-associated pathologies by immunohistochemistry and amyloid beta (Aβ) peptidomics. We demonstrated that a disease-associated PC subset (PC2) expanded in AD patients compared to age-matched, cognitively unimpaired controls. Surprisingly, we found that this increase in the percentage of PC2 (%PC2) was correlated negatively with BBB breakdown in AD patients, unlike in natural aging or other reported disease conditions. The higher %PC2 in AD patients was also correlated with a lower Aβ42 plaque load and a lower Aβ42:Aβ40 ratio in the brain as determined by immunohistochemistry. Colocalization analysis of multicolor confocal immunofluorescence microscopy images suggests that AD patient with low %PC2 have higher BBB breakdown due to internalization of Aβ42 by the physiologically normal PC subset (PC1) and their concomitant cell death leading to more vessels without PCs and increased plaque load. On the contrary, it appears that PC2 can secrete cathepsin D to cleave and degrade Aβ built up outside of PC2 into more soluble forms, ultimately contributing to less BBB breakdown and reducing Aβ plaque load. Collectively our data shows functionally distinct mechanisms for PC1 and PC2 in high Aβ conditions, demonstrating the importance of correctly identifying these populations when investigating the contribution of neurovascular dysfunction to AD pathogenesis., (© 2024 The Author(s). Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Pediatric central nervous system (CNS) tumors represent one of the most intricate challenges faced by children and their families in the context of cancer illness. In Italy, the psychosocial working group (GDL) of the AIEOP, composed by professionals (psycho-oncologists/neuropsychologists) involved in the care pathways of patients with CNS tumors, has initiated a consensus process regarding the psychological/neuropsychological assessment of CNS patients to improve accessibility to standardized and shared protocols. Standardized psychological and neuropsychological instruments are proposed in the document, which provides for a selection in a tailor-made approach that is simultaneously shared by various centers.

Background: Venous thromboembolism frequently complicates orthopedic surgery. The aim of the study was to evaluate the overall incidence, site, and risk factors for venous thromboembolism in patients undergoing hip fracture surgery in DVT prophylaxis according to guidelines recommendations. Methods: Standard ultrasonography (CUS) was performed in the 5-6th postoperative day in all patients who underwent hip fracture surgery between 1 January and 31 December 2019. Pharmacological prophylaxis was started within 12 h from admission. In the first half of the year, dalteparin (5000 IU/day) was available while nadroparin (38 IU/kg until 3rd postoperative day and thereafter 57 IU/kg) was available in the second part of the year. Results: A total of 505 patients, 144 males and 361 females, with a mean age of 84 years, entered in the study. Post-operative DVT was found at screening ultrasonography in 121 patients (24%). Most involved distal veins (91) while proximal DVT occurred in 30. Two patients had not fatal pulmonary embolism (0.3%). Time to surgery ( p = 0.0009) and ≥2 comorbidities ( p = 0.0198) were independent predictive factors of DVT. Moreover, dalteparin prophylaxis was associated with a 1.7-times higher risk of developing a DVT compared to nadroparin. Conclusions: DVT occurs in 24% of patients after hip fracture surgery despite thromboprophylaxis. Time to surgery and ≥2 comorbidities were independent risk factors. The protective effects of nadroparin should be confirmed by a randomized trial. All patients with DVT were discharged with indication to anticoagulation for at least three months.

Russell's diencephalic syndrome is a set of signs and symptoms characterized by extreme weight loss, with no impairment of height or head circumference, without changes in intake or appetite. It is due to hypothalamic dysfunction associated with space-occupying lesions in this region. It is a rare cause of malnutrition in pediatrics, so its diagnosis is often delayed. Here we describe the case of a 17-month-old male patient with weight loss for 3 months who was admitted to the pediatric inpatient ward due to suspected intestinal malabsorption syndrome. After ruling out the most common causes of malnutrition, the patient was diagnosed with pilomyxoid astrocytoma of the brainstem., (Sociedad Argentina de Pediatría.)

The formation of amyloid-β (Aβ) aggregates in brain is a neuropathological hallmark of Alzheimer's disease (AD). However, there is mounting evidence that Aβ also plays a pathogenic role in other types of dementia and that specific post-translational Aβ modifications contribute to its pathogenic profile. The objective of this study was to test the hypothesis that distinct types of dementia are characterized by specific patterns of post-translationally modified Aβ variants. We conducted a comparative analysis and quantified Aβ as well as Aβ with pyroglutamate (pGlu3-Aβ and pGlu11-Aβ), N-truncation (Aβ(4-X)), isoaspartate racemization (isoAsp7-Aβ and isoAsp27-Aβ), phosphorylation (pSer8-Aβ and pSer26-Aβ) or nitration (3NTyr10-Aβ) modification in post mortem human brain tissue from non-demented control subjects in comparison to tissue classified as pre-symptomatic AD (Pre-AD), AD, dementia with Lewy bodies and vascular dementia. Aβ modification-specific immunohistochemical labelings of brain sections from the posterior superior temporal gyrus were examined by machine learning-based segmentation protocols and immunoassay analyses in brain tissue after sequential Aβ extraction were carried out. Our findings revealed that AD cases displayed the highest concentrations of all Aβ variants followed by dementia with Lewy bodies, Pre-AD, vascular dementia and non-demented controls. With both analytical methods, we identified the isoAsp7-Aβ variant as a highly abundant Aβ form in all clinical conditions, followed by Aβ(4-X), pGlu3-Aβ, pGlu11-Aβ and pSer8-Aβ. These Aβ variants were detected in distinct plaque types of compact, coarse-grained, cored and diffuse morphologies and, with varying frequencies, in cerebral blood vessels. The 3NTyr10-Aβ, pSer26-Aβ and isoAsp27-Aβ variants were not found to be present in Aβ plaques but were detected intraneuronally. There was a strong positive correlation between isoAsp7-Aβ and Thal phase and a moderate negative correlation between isoAsp7-Aβ and performance on the Mini Mental State Examination. Furthermore, the abundance of all Aβ variants was highest in APOE 3/4 carriers. In aggregation assays, the isoAsp7-Aβ, pGlu3-Aβ and pGlu11-Aβ variants showed instant fibril formation without lag phase, whereas Aβ(4-X), pSer26-Aβ and isoAsp27-Aβ did not form fibrils. We conclude that targeting Aβ post-translational modifications, and in particular the highly abundant isoAsp7-Aβ variant, might be considered for diagnostic and therapeutic approaches in different types of dementia. Hence, our findings might have implications for current antibody-based therapies of AD., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Consent for publication: All the authors have approved publication., (© 2024. The Author(s).)

The aim of this scoping review is to describe the role, education, policies/regulation, skills and competencies required for advanced practice in paediatric haematology-oncology nursing in Europe, highlighting the differences in development between the different European countries. A scoping review was conducted following the methodological framework of guidelines by Arksey and O'Malley and the recommendations for advancing the methodology by Levac et al. We searched MEDLINE/PubMed, EMBASE, CINAHL, Cochrane Library, Scopus, grey literature, webpages, reference lists and performed a manual search, without any restrictions on language or time. The intersection between databases, grey literature and evidence documents traced from the sites of the most authoritative European organisations in the field made it possible to identify the regulatory and training differences between the various countries that were examined. This scoping review highlights how advanced knowledge and competences are used in the care of paediatric haematology-oncology patients, which are strictly necessary for implementing quality care. At present these competences are not recognised in policies and regulation in most of the countries that were examined. It is desirable that all EU member states work to implement a radical change and allow these more competent figures to assist patients in the best possible way., (© 2024 Wiley Periodicals LLC.)

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the ITM2B gene (also known as BRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer's disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. The ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. The pathological examination of post-mortem tissue supports the presence of ABri in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. These data have implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer's disease., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to evaluate the effect of extrusion and of open-pan cooking on whole germinated and non-germinated grains of pearl millet (Pennisetum glaucum L. R. Br.), on its chemical-nutritional composition and in vitro iron bioavailability. The experimental design consisted of three flours: non-germination open-pan cooked millet flour (NGOPCMF), germination open-pan cooked millet flour (GOPCMF), and extrusion cooked millet flour (ECMF). The ECMF increased the carbohydrates, iron, manganese, diosmin, and cyanidin and decreased the total dietary fiber, resistant starch, lipids, and total vitamin E, in relation to NGOPCMF. The GOPCMF increased the lysine and vitamin C and decreased the phytate, lipids, total phenolic, total vitamin E, and riboflavin concentration, in relation to NGOPCMF. Furthermore, germinated cooked millet flour and extruded millet flour improved iron availability in vitro compared to non-germinated cooked millet flour. GOPCMF and ECMF generally preserved the chemical-nutritional composition of pearl millet and improved in vitro iron bioavailability; therefore, they are nutritionally equivalent and can be used to develop pearl millet-based products., Competing Interests: Declaration of competing interest The authors affirm that they have no known conflicting financial interests or personal relationships that may have influenced the research presented in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The design of new hydrophobic solvents is essential for replacing the toxic hexane for extracting nonpolar compounds such as fatty acids. On the other hand, the full use of plant matrices seeking to obtain new food and pharmaceutical products from their coproducts has also been the focus of sustainable processes. This study proposed new solvents for replacing hexane to extract fatty acids and hydrophobic bioactive compounds from coproducts obtained from almond- and peanut-based milk processing. The COSMO-RS method was used to select terpene-based mixtures to substitute hexane. Experimentally, four liquid solvents were formed from 1:2 tetradecanol/1,8-cineole (TE/EU), 1:2 camphor/1,8-cineole (CA/EU), 1:1 oleic acid/1,8-cineole (OL/EU), and 1:1 menthol/1,8-cineole (ME/EU). DSC analyses indicated the reduction of the CA/EU, OL/EU, and ME/EU melting points concerning their components. However, the melting point values predicted by the COSMO for obtaining eutectic mixtures differed. CA/EU was the only mixture with a melting point lower than the COSMO-RS-predicted one. In contrast, the FTIR spectra did not provide a clear visualization of the hydrogen bond formation between camphor and 1,8-cineole. This could be due to the formation of weak hydrogen bonds, a phenomenon observed in other studies. Nevertheless, these solvents have the advantage of low viscosity, a promising feature that likely facilitated mass transfer in the extraction of hydrophobic compounds from almond and peanut coproducts. ME/EU provided the same global extraction yield as hexane and higher phytosterol extraction from almond coproducts. On the other hand, CA/EU provided the same global yield and squalene content as hexane from peanut coproducts. The extracts can be directly used in food and pharmaceutical applications since the solvents are usually part of the formulations. However, DSC and TGA-DTA analyses indicated possible ways to separate the solvents., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Pomegranate ( Punica granatum L.) peel is a potential source of bioactive phenolic compounds such as ellagic acid and α- and β-punicalagin. This work explores the efficiency of natural deep eutectic solvents combined with ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) for their extraction. Five NaDESs were evaluated by employing UAE (25 °C, for 50 min) to determine their total phenolic content (Folin-Ciocalteu assay) and ellagic acid and α- and β-punicalagin contents (high-performance liquid chromatography (HPLC-DAD)). The NaDES composed of choline chloride (ChCl) and glycerol (Gly) (1:2, molar ratio) was the most efficient in the UAE when compared with the rest of the NaDESs and water extracts. Therefore, ChCl:Gly was further evaluated using PLE at different temperatures (40, 80, 120 and 160 °C). The PLE-NaDES extract obtained at 80 °C for 20 min at 1500 psi exhibited the highest contents of ellagic acid and α- and β-punicalagin compared to the rest of the temperatures and PLE-water extracts obtained under the same extraction conditions. Combining UAE or PLE with a NaDES emerges as a sustainable alternative for extracting ellagic acid and α- and β-punicalagin from pomegranate peel.

We propose an innovative approach to address the pressing need for efficient and transparent evaluation techniques to assess extraction processes' sustainability. In response to society's growing demand for natural products and the consequent surge in biomass exploration, a critical imperative arises to ensure that these processes are genuinely environmentally friendly. Extracting natural compounds has traditionally been regarded as a benign activity rooted in ancient practices. However, contemporary extraction methods can also significantly harm the environment if not carefully managed. Recognizing this, we developed a novel metric, Path2Green , tailored specifically and rooted in 12 new principles of a green extraction process. Path2Green seeks to provide a comprehensive framework beyond conventional metrics, offering a nuanced understanding of the environmental impact of extraction activities from biomass collection/production until the end of the process. By integrating factors such as resource depletion, energy consumption, waste generation, and biodiversity preservation, Path2Green aims to offer a holistic assessment of sustainability of an extraction approach. The significance of Path2Green lies in its ability to distill complex environmental data into a simple, accessible metric. This facilitates informed decision-making for stakeholders across industries, enabling them to prioritize greener extraction practices. Moreover, by setting clear benchmarks and standards, Path2Green incentivizes innovation and drives continuous improvement in sustainability efforts, being a new user-friendly methodology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Citrus fruits (CF) are highly consumed worldwide, fresh, processed, or prepared as juices and pies. To illustrate the high economic importance of CF, the global production of these commodities in 2021 was around 98 million tons. CF's composition is considered an excellent source of phenolic compounds (PC) as they have a large amount and variety. Since ancient times, PC has been highlighted to promote several benefits related to oxidative stress disorders, such as chronic diseases and cancer. Recent studies suggest that consuming citrus fruits can prevent some of these diseases. However, due to the complexity of citrus matrices, extracting compounds of interest from these types of samples, and identifying and quantifying them effectively, is not a simple task. In this context, several extractive and analytical proposals have been used. This review discusses current research involving CF, focusing mainly on PC extraction and analysis methods, regarding advantages and disadvantages from the perspective of Green Chemistry.

Aims: The aggregation and deposition of amyloid-β (Aβ) peptides in the brain is thought to be the initial driver in the pathogenesis of Alzheimer's disease (AD). Aside from full-length Aβ peptides starting with an aspartate residue in position 1, both N-terminally truncated and elongated Aβ peptides are produced by various proteases from the amyloid precursor protein (APP) and have been detected in brain tissues and body fluids. Recently, we demonstrated that the particularly abundant N-terminally truncated Aβ4-x peptides are generated by ADAMTS4, a secreted metalloprotease that is exclusively expressed in the oligodendrocyte cell population. In this study, we investigated whether ADAMTS4 might also be involved in the generation of N-terminally elongated Aβ peptides., Methods: We used cell-free and cell-based assays in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) and electrochemiluminescence sandwich immunoassays to identify and quantify N-terminally elongated Aβ peptide variants. Antibodies against these Aβ variants were characterised by peptide microarrays and employed for the immunohistochemical analyses of human brain samples., Results: In this study, we discovered additional ADAMTS4 cleavage sites in APP. These were located N-terminal to Asp-(1) in the Aβ peptide sequence between residues Glu-(-7) and Ile-(-6) as well as Glu-(-4) and Val-(-3), resulting in the release of N-terminally elongated Aβ-6-x and Aβ-3-x peptides, of which the latter serve as a component in a promising Aβ-based plasma biomarker. Aβ-6/-3-40 peptides were detected in supernatants of various cell lines and in the cerebrospinal fluid (CSF), and ADAMTS4 enzyme activity promoted the release of Aβ-6/-3-x peptides. Furthermore, by immunohistochemistry, a subset of AD cases displayed evidence of extracellular and vascular localization of N-terminally elongated Aβ-6/-3-x peptides., Discussion: The current findings implicate ADAMTS4 in both the pathological process of Aβ peptide aggregation and in the early detection of amyloid pathology in AD., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

The main motivation for this research was to improve the properties of geopolymers by reinforcement using synthetic and natural fibers, and to gain new knowledge regarding how the nature and/or the quantity of reinforcement fibers influences the properties of the final geopolymers. The main objective was to investigate the effects of different types of reinforcement fibers on the properties of the geopolymers. These reinforcement fibers were mainly environmentally friendly materials that can be used as alternatives to ordinary Portland cement. The authors used fly ash and river sand as the raw materials for the matrix, and added carbon fibers (CF), flax fibers (FF), or a hybrid of both (CFM) as reinforcements. The samples were prepared by mixing, casting, and curing, and then subjected to various tests. The main research methods used were compressive strength (CS), flexural strength (FS), water absorption (WA), abrasion resistance (Böhme's disk method), microstructure analysis (SEM), chemical composition (XRF), and crystal structure analysis (XRD). The results showed that the addition of fibers partially improved the mechanical properties of the geopolymers, as well as reducing microcracks. The CF-reinforced geopolymers exhibited the highest compressive strength, while the FF-reinforced geopolymers showed the lowest water absorption. The authors, based on previous research, also discussed the factors that influence fiber-matrix adhesion, and the optimal fiber content for geopolymers.

Background: Music Therapy (MT) is a non-pharmacological, art-based intervention that employs music experiences within a therapeutic alliance to attend to clients' physical, emotional, cognitive, and social requirements. This is the first study aiming at investigating the impact of MT on the psychological facets of children suffering from cancer., Methods: The study, combining the AQR and m-YPAS assessment tools, evaluated behavioral, sound-musical, and interactive parameters in pediatric oncology patients undergoing MT sessions during hospitalization. Fifty patients admitted to the Paediatric Oncology and Haematology Unit at Policlinico S. Orsola Hospital in Bologna, Italy, were enrolled, irrespective of their treatment regimen. Data collection occurred on the first day of the MT session between 3 p.m. and 5 p.m., with observations conducted by independent observers. In addition to traditional statistical analysis, network analysis was used to explore the combined interactions of all parameters, effectively discerning the distinctive roles played by each one during therapy sessions and their influence on all others., Results: Network analysis highlighted distinct patterns of interactions among parameters during the various sessions, emphasizing the role of positive emotions and a calm setting, the child's ability to take the initiative in sessions, their sense of agency, and the parent's role in guiding them. Significant differences were recorded at each time point between all variables considered., Conclusions: The results of this innovative study may pave the way for future multicenter studies aimed at further exploring the role of MT in children undergoing both curative and palliative treatments for cancer.

Purpose: Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture., Patients and Methods: A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL., Results and Conclusions: TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A ( p <0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; p =0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia)., Conclusion: DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Rostagno et al.)

Neuropsychiatric symptoms, depression, and progressive mental confusion should not be overlooked as onset symptoms of multiple cerebral ischemic lesions due to cardiac embolization. Comprehensive clinical evaluation due to progressive anemia led to the diagnosis of poorly differentiated adenocarcinoma of the esophagogastric junction as cause of embolizing nonbacterial mitral endocarditis., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Hesperidin is a phenolic compound usually found in citrus fruits, which is known for its anti-inflammatory and antioxidant properties. This bioactive compound has already been used to formulate medications to treat chronic venous insufficiency. In this work, through a system which allows the in-line coupling of the pressurized liquid extraction (PLE) and high-intensity ultrasound (HIUS) with solid phase extraction (SPE), and analysis by high-performance liquid chromatography with UV-Vis detector (HPLC-UV) in on-line mode, a method was developed to obtain, separate, and quantify hesperidin from the industrial waste of lime. An eco-friendly approach with water and ethanol as extraction solvents was used. Parameters such as temperature (80, 100, and 120 °C) and HIUS power (0, 200, and 400 W) were evaluated regarding hesperidin yield. In this context, the higher hesperidin yield (18.25 ± 1.52 mg/g) was achieved using water at a subcritical state (120 °C and 15 MPa). The adsorbent Sepra TM C-18-E isolated hesperidin from the other extracted compounds employing 50% ethanol in the SPE elution. The possibility ofon-lineanalysis coupling a high-performance liquid chromatograph to an ultraviolet detector (HPLC-UV) system was studied and shown to be a feasible approach for developing integrated technologies. Conventional extractions and their antioxidant capacities were evaluated, highlighting the advantages of the HIUS-PLE-SPE extractive method. Furthermore, the on-linechromatographic analysis showed the potential of the HIUS-PLE-SPE- HPLC-UV system to quantify the extracted compounds in real time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study assessed the effects of hydroxytyrosol (HT) on 8- to 20-day-old broilers challenged with lipopolysaccharide (LPS); 180 Cobb500™ male chicks were randomly assigned to 3 treatment groups, each comprising 10 replicates with 6 birds per replicate. Treatments included a control diet (CON), CON with LPS administration, and CON + LPS supplemented with 10 mg of HT/kg of feed. LPS was administered intraperitoneally on days 14, 16, 18, and 20. Body weight (BW), body weight gain (BWG), and the feed conversion ratio (FCR) were measured. On day 20, ten birds per treatment were slaughtered for analysis. Bursa, spleen, and liver were collected, and their respective relative weight was determined. The jejunum was destined for morphological analyses of villus height (VH), crypt depth (CD), and their ratio (VH:CD), and for mRNA expression of nuclear factor kappa B (NF-κB), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and interleukins 10 (IL-10), 1 beta (IL-1β), and 8 (IL-8). HT improved BW, BWG, and FCR, and reduced crypt depth (CD) while increasing the VH:CD ratio in the jejunum. Moreover, HT downregulated mRNA expression of CAT, GPx, IL-10, and IL-1β. In conclusion, HT enhances broiler growth performance, mitigates jejunal mucosa damage from LPS, and modulates antioxidant and immune responses.

Every year, not less than 300 million non-cardiac surgery interventions are performed in the world. Perioperative mortality after non-cardiac surgery is estimated at 2% in patients over 45 years of age. Cardiovascular events account for half of these deaths, and most are due to perioperative myocardial infarction (MINS). The diagnosis of postoperative myocardial infarction, before the introduction of cardiac biomarkers, was based on symptoms and electrocardiographic changes and its incidence was largely underestimated. The incidence of MINS when a standard troponin assay is used ranges between 8 and 19% but increases to 20-30% with high-sensitivity troponin assays. Higher troponin values suggesting myocardial injury, both with or without a definite diagnosis of myocardial infarction, are associated with an increase in 30-day and 1-year mortality. Diagnostic and therapeutic strategies are reported.

Carnosic (CA) and rosmarinic (RA) acids are the primary phenolic acids in hydrophilic rosemary extracts. Their combination exhibits high antioxidant activity and can be explored in several applications. This study aimed to develop an extraction procedure using bio-based solvents to recover two rosemary extracts, one rich in CA and the other in RA. By using ultrasound-assisted extraction (UAE) and a pool of 34 solvents, we evaluated nominal power (W), extraction time (min), and solvent water percentage (% H 2 O) regarding yield and selectivity. The authors propose a sequential UAE procedure validated by applying ethanol 99.5 % (v/v), 240 W, and 5 min to recover a rich fraction of 24.0 mg CA .g biomass -1 ; followed by a second step using AmAc:LA (1:2 M ratio), 20 % H 2 O (m/m), 320 W, and 5 min that resulted in 8.4 mg RA .g biomass -1 . Our results indicate that modulating the solvent composition and process temperature is critical to increasing extraction yields and selectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study produced pH-sensing carboxymethyl cellulose (CMC) films functionalized with bioactive compounds obtained by pressurized liquid extraction (PLE) of grape peel to monitor the freshness of pork and milk. A semi-continuous PLE was conducted using hydroethanolic solution (70:30, v/v) at a flow rate of 5 mL/min, 15 MPa, and 60 °C. The films were produced by the casting technique using CMC (2.5 %, w/v), glycerol (1 %, v/v), and functionalized with 10, 30, and 50 % (v/v) grape peel extract. From the results obtained, LC-MS/MS revealed that PLE extracted twenty-seven phenolic compounds. The main phenolic compounds were kaempferol-3-glucoside (367.23 ± 25.88 µg/mL), prunin (270.23 ± 3.62 µg/mL), p-coumaric acid (236.43 ± 26.02 µg/mL), and procyanidin B1 (117.17 ± 7.29 µg/mL). The CMC films presented suitable color and mechanical properties for food packaging applications. The addition of grape peel extract promoted the pH-sensing property, showing the sensitivity of anthocyanins to pH changes. The films functionalized with grape peel extract presented good release control of bioactive compounds, making them suitable for food packaging applications. When applied to monitor the freshness of pork and milk, the films exhibited remarkable color changes associated with the pH of the food during storage. In conclusion, PLE is a sustainable approach to obtaining bioactive compounds from the grape peel, which can be applied in the formulation of pH-sensing films as a promising sustainable material to monitor food freshness during storage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To identify the core competencies of the pediatric hematology-oncology nurse., Methods: A Delphi study was conducted. After identifying the competencies of the pediatric hematology-oncology nurse through a literature review, a questionnaire was created to be administered to a panel of experts to obtain consensus. The panel of experts consisted of 19 nurses. For each competence identified, it was necessary to evaluate the competence in terms of "understanding" and "relevance", assigning a score from 0 (not at all) to 4 (completely), according to a Likert scale. Then, the experts identified what could be the necessary "level of work experience" within which a nurse should become autonomous in every competency choosing among the levels: beginner, intermediate, expert. Consensus among the experts was reached in two rounds., Results: After submitting the document to two rounds, a final document was obtained with a total of 126 competencies, divided into nine areas. Fifty-eight competencies fall into the "beginner" level, 46 competencies into the "intermediate" level and 22 competencies into the "expert" level., Conclusions: The document produced by this study could be a starting point for organizing specific training courses for nurses in the pediatric hematology-oncology department. A clear description of specific competencies for pediatric hematology-oncology nurses would help ensure the best care for the child., Competing Interests: Declaration of competing interest The authors declare no existing conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study proposed an integrated and automated procedure to extract, separate, and quantify bioactive compounds from a coffee co-product by pressurized liquid extraction (PLE) coupled inline with solid phase extraction (SPE) and online with HPLC-PDA (PLE-SPE × HPLC-PDA). The efficiency of the two-dimensional system in performing real-time analysis was verified by comparing HPLC-PDA results acquired by the system (online) and carried out after the extract fraction collection (offline). Different flow rates (1.5 mL/min for 336 min, 2 mL/min for 246.4 min, and 2.5 mL/min for 201.6 min) were evaluated to optimize the extraction, separation, and analysis method by PLE-SPE × HPLC-PDA. Subcritical water at 125 °C and 15 min of static time allowed the highest extraction yields of caffeine and 5-caffeoylquinic acid (5-CQA). Caffeine was retained during the aqueous extraction in the SPE adsorbent and eluted from the column by exchanging the solvent for a hydroethanolic mixture. Thus, caffeine was separated from 5-CQA and other phenolic compounds, producing extracts with different compositions. The solvent flow rate did not have a significant effect (p-value ≥ 0.05) on the extraction, separation, and analysis (by online and offline methods) of 5-CQA. However, the online quantification of retained compounds in the SPE (i.e., caffeine) can underestimate concentration compared to offline analysis. Nevertheless, the results suggest that coupling of advanced techniques can be used to efficiently extract, separate, and analyze fractions of phenolic compounds, supplying an integrated method to produce high-added value ingredients for several applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels., Methods: The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed., Results: The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison., Conclusions: Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed., (© 2023 John Wiley & Sons Ltd.)

The study aimed to evaluate the effects of dietary supplementation of hydroxytyrosol (HT) on performance, fat, and blood parameters of broilers. In total, 960 male chicks were distributed into four treatments groups with 12 replicates with 20 birds per pen, with varying HT levels (0, 5, 10, and 50 mg/kg of feed) added to the basal diet from 1 to 42 days old. Feed intake, body weight gain, and feed conversion ratio were evaluated. Enzymes related to liver injury were evaluated in blood. Fatty acid profile and malondialdehyde (MDA) concentration were determined in the breast meat. Dietary supplementation of HT did not improve broilers' performance ( p > 0.05). Birds fed 50 mg HT/kg had lower AST, ALT, and GGT concentrations ( p ≤ 0.05), whereas broilers fed 5, 10, and 50 mg HT/kg, had lower TBIL concentrations ( p ≤ 0.05). Breast meat of broilers fed 50 mg HT/kg had lower lipid content, saturated fatty acid, unsaturated fatty acids, MDA concentrations ( p ≤ 0.05), and polyunsaturated fatty acids ( p < 0.0001). In summary, supplementation of 5, 10, and 50 mg HT/kg does not improve the performance of broilers, but the dose of 50 mg HT/kg helps the liver against inflammation and improves fat parameters.

Cardiac involvement, such as myocarditis and pericarditis, can be a severe complication of monkeypox virus (mpox) infection and could be related to other co-infections with cardiac involvement. Tecovirimat is an antiviral specifically designed to inhibit smallpox infection diffusion and approved by the FDA for other Orthopoxvirus infections; its efficacy in mpox-infected patients is not well established. We present the case of a cardiac complication during mpox infection in a previously undiagnosed Lyme disease in a 42-year-old man living with HIV. Two days after the typical maculopapular rash, the patient reported a rise in body temperature up to 39 °C, chest pain without irradiation, and shortness of breath. We found an increase in troponin level, a slight reduction in ejection fraction, and grade 2 AV block (Mobitz 1 and 2) with frequent sinus pauses (the longest of 10.1 s). Given the suspicion of myopericarditis with cardiac conduction system involvement, the patient was admitted to the Intermediate Care Unit for continuous monitoring and further evaluation. Treatment included Ibuprofen 600 mg every 12 hours (bid) and colchicine 1 mg once daily for anti-inflammatory purposes. Concomitantly, treatment with tecovirimat was started at 600 mg bid for a total of 14 days. Cardiac MRI with gadolinium showed mild interstitial edema and pericardial enhancement. However, despite the clinical and laboratory resolution of the acute phase, bradycardia with episodes of AV block persisted at follow-up, suggesting the possibility of an additional etiology. Thus, the patient was investigated for Lyme disease because high-degree AV block is the most common presentation of Lyme carditis. Serological results evidenced a previous Borrelia burgdorferi senso latu. We decided to start treatment with doxycycline 100 mg every 12h, even pending the uncertainty of the role of a previous Lyme disease in determining the cardiac rhythm disturbances. At the evaluation on day 44, the patient was systemically well, and after cardiologist consultation, pace-maker implantation was not deemed indicated. This case underscores the importance of considering alternative causes of carditis when the clinical picture remains unclear or persists after the acute phase., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Professor L. Zammarchi currently serves as associate editor to the Infectious Diseases and Global Health section of the Journal If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Few data are available about results after procedures of resection and megaprosthesis at the hip in very elderly patients. The aim of our study was to ascertain survival and complications in patients aged 80 or older undergoing these major orthopedic procedures. A consecutive series of 27 procedures in 26 patients aged 80-93 years was evaluated. In total, 15 procedures were performed due to oncological diseases, 6 were performed following joint arthroplasty failures or periprosthetic fractures, and 6 were performed after trauma or trauma sequelae. Survival of the patients ranged from 0 to 122 months. Overall survival was 56% at 3 years, 24% at 5 years, and 16% at 8 years. An early postoperative death during the first 3 months occurred in five patients (18.5%). The only preoperative parameter negatively affecting survival was preoperative hemoglobin lower than 11 g/dL. Local complications were similar to reported rates in all-age patients' series. In our experience, resection and megaprosthetic reconstruction can also be a valid choice in very elderly patients, with 56% of patients living more than two years from surgery and 24% more than five. Nevertheless, early postoperative deaths are frequent. A multidisciplinary evaluation of frailty of the patient must be accomplished, and patients and relatives must be informed about the risks of the procedure.

This work developed a universal UPLC-PDA method based on safe reagents to analyze anthocyanins from different foods. Nine foods were studied by the developed chromatographic method, which was constructed using a solid core C18 column and a binary mobile phase composed of (A) water (0.25 mol citric acid .L solvent -1 ), and (B) ethanol. A total running time of 6 min was obtained, the faster comprehensive method for anthocyanins analysis. Mass spectrometry analysis was employed to identify a comprehensive set of 53 anthocyanins comprising glycosylated and acylated cyanidin, pelargonidin, malvidin, peonidin, petunidin, and delphinidin derivatives. Cyanidin-3-O-glucoside (m/z + 449) and cyanidin-3-O-rutinoside (m/z + 595) were used as standards to validate the accuracy of the developed method. The analytical parameters were evaluated, including intra-day and inter-day precision, robustness, repeatability, retention factor (k), resolution, and peak symmetry factor. The current method demonstrated excellent chromatographic resolution, making it a powerful tool for analyzing anthocyanins pigments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

(1) Background: Little prospective data exist regarding the perioperative management and long-term prognosis of elderly patients receiving treatment with antithrombotic drugs and undergoing urgent surgery for a hip fracture. (2) Methods: The study included patients who required hip surgery and were receiving warfarin, DOAc or P2Y12 antiplatelet agents at the moment of trauma. Ongoing antithrombotic treatment was managed according to existing recommendations. The endpoints of the study were the time to surgery, perioperative bleeding, the need for transfusion and, finally, mortality, major cardiovascular events and re-hospitalization at 6 and 12 months. (3) Results: The study included a total of 138 patients. The mean age was 86 years; 75.4% were female. Eighty-two received DOAc, thirty-six received warfarin and twenty received P2Y12 inhibitors. The controls were 283 age- and sex-matched patients who did not receive antithrombotic treatment. A total of 38% of patients receiving warfarin underwent surgery <48 h, 52% receiving DOAc, 55% receiving P2Y12 inhibitors and, finally, 82% in the control group. Perioperative bleeding and the need for transfusion were not different between the four groups. Mortality at 6 months was higher in patients receiving warfarin and P2Y12 inhibitors (30% and 25%) in comparison to DOAc and the control group (11.6% and 10% p < 0.0001). Similarly, the other endpoints were more frequent in patients receiving warfarin and P2Y12 inhibitors. The trend was maintained for 12 months. No significant differences in mortality were found between early (<48 h) and late (>48 h) surgery independent of the type of treatment. (4) Conclusions: Our study confirmed that anticoagulants delay surgery in patients with hip fractures; however, intervention > 48 h is not associated with a poorer prognosis. This finding is relevant as it underlines that, in patients at high risk of postoperative cardiovascular complications, the careful management of anticoagulation before surgery may compensate for the delay of surgery with a very low in-hospital mortality rate (<1%). One-year survival was significantly lower in patients receiving warfarin, probably related to their worse risk profile at the moment of trauma survival.

Introduction: Although clinical guidelines suggest echocardiography before surgery in patients with hip fracture, no prospective studies exist in the literature. The aim of the present investigation was to assess whether preoperative echocardiography affects time to surgery, length of hospital stay (LOS), and in hospital mortality in high-risk patients who need surgery for a hip fracture., Material and Methods: In the study entered 255 consecutive patients with hip fracture referred to a multidisciplinary hip fracture unit. Seven hundred seventeen patients referred before the implementation of routine echocardiographic examination were considered as control group. Echocardiography was performed in patients with systolic murmurs, unstable clinical conditions, recent decompensation of heart failure or hospital admission for coronary disease. Time to surgery, LOS, and in hospital mortality in patients who underwent preoperative echocardiography (high-risk group) were compared with patients who did not undergo echo (low-risk group) and with the control group., Results: 122/255 patients underwent echocardiography. The two groups did not differ for age, sex, type or fracture, and notably time to surgery and LOS. Coronary heart disease, atrial fibrillation, and two or more comorbidities were more frequent in the echo group. Overall clinical characteristics were not different from group of patients referred before the implementation of the echocardiographic protocol but in these last patients time to surgery and LOS were significantly longer. As well in hospital mortality was not significantly different in the two groups (1.9 in echo vs. 1.7% in nonecho) but lower than in the control group (4.1% )., Conclusions: An echocardiographic guide may be useful in a high-risk group with a hip fracture to choose the proper anesthetic setting, referral for intensive care observation after surgery and, optimal medical treatment, including fluid management without delay in time to surgery., Competing Interests: The authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Caring is an essential value in nursing, it's crucial in pediatric hemato-oncology: we tested the Nurse Caring Behavior Scale (NCBS) in this setting. Methods: The NCBS is a 14-item validated psychometric questionnaire: caregivers and nurses adapted versions were used. Descriptive statistics and exploratory factor analysis (EFA) were used. Results: The questionnaires were completed by 188 caregivers and 193 nurses. The two data sets were suitable for EFA and fitted with one-solution factor analysis; factor loading showed values >0.40 (>0.60 for caregivers). The mean scores were: 4.5 (range: 1-5) for caregivers and 4.7 (range: 1-5) for nurses. Conclusion: The two validated versions can be used on a wider nurses and caregivers sample and provide an instrument for the development of nursing protocols based on caring., (© Copyright 2023 Springer Publishing Company, LLC.)

Analyzing compounds such as polyphenols in solid samples frequently uses a solid-liquid extraction step. The solid-liquid extraction and analysis integration in a single equipment is not commercially available since several challenges are inherent to this hybridization. In the context of developing more sustainable analytical procedures, innovative techniques are demanded. Given that, this work proposes a new integrative system (2D PLE × HPLC-PDA) and presents its validation for bioactive compound extraction and online quantification, discussing the main advantages and cares that need to be taken. Two food byproducts - passion fruit bagasse and coffee husks - were chosen as solid model samples. The system was configured to perform pressurized liquid extraction (PLE) with periodical automated extract injection in the HPLC, consequently obtaining the online quantification of target compounds from the solid samples. In parallel with the online injections, extract fractions were collected and submitted to offline analysis in which the extraction yield of piceatannol and chlorogenic acid and caffeine were evaluated, respectively, for passion fruit bagasse and coffee husks. The extraction yields obtained by online and offline injections were compared and were significantly equal (p > 0.05). Thus, the 2D PLE × HPLC-PDA system represents a feasible tool to integrate solid sample preparation and chemical analysis of biocompounds in a single and online step., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background : There is minimal information regarding sleep disturbance and burnout during COVID-19 in nurses working within haematology-oncology and hematopoietic stem cell transplantation (HSCT) settings. Aim : To identify socio-demographic and professional factors that predicted burnout and sleep disturbance during COVID-19 in nurses working in HSCT settings. Design/Methods : Data were collected using the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index. Descriptive statistics and linear regression examined relationships. Results : 308 responses were received. Nurses working in outpatient settings had greater emotional exhaustion (Rpartial = -0.12, n  = 308, p  = 0.03). Negative predictors for quality of sleep were transplant programme setting (Rpartial = -0.19, n  = 308, p  < 0.01) and years working in HSCT (Rpartial = -0.17, n  = 308, p  < 0.01). Other relationships were found on univariate analysis. Conclusion : Institutions must offer programmes for nurses to develop sleep strategies, self-care, and work-related stress management.

Metabolism and digestibility trials were performed on broiler chickens to determine 1) nitrogen-corrected apparent metabolizable energy (AMEn) using total excreta collection and 2) standardized ileal amino acid digestibility (SIAAD) using the ileal digesta collection from high-protein dried distillers' grains (HP-DDG) and corn bran with solubles (CBS). The results of the metabolism trial indicated that AMEn values for HP-DDG and CBS were 3,334 kcal/kg and 2,083 kcal/kg on dry matter (DM) basis, respectively. Concerning the HP-DDG, the digestibility trial resulted in the following SIAAD values and digestible concentrations, respectively: 80.33% and 1.09 for Lys, 85.95% and 1.44 for Met + Cys, 75.58% and 1.24 for Thr, 89.58% and 1.66 for Arg, 84.91% and 1.08 for His, 86.37% and 1.35 for Ile, 90.64% and 4.56 for Leu, 85.76% and 1.80 for Val, and 88.67% and 1.90 for Phe. Concerning the CBS, the following SIAAD values and digestible concentrations were measured, respectively: 79.29% and 0.44 for Lys, 89.57% and 0.31 for Met + Cys, 78.89% and 0.40 for Thr, 92.28% and 0.66 for Arg, 87.48% and 0.36 for His, 93.40% and 0.35 for Ile, 92.27% and 1.01 for Leu, 90.97% and 0.51 for Val, and 88.81% and 0.45 for Phe. The digestibility average of CBS is 88.45% for essential amino acids and 85.21% for nonessential amino acids, whereas the digestibility average of HP-DDG is 85.83% for essential amino acids and 83.83% for nonessential amino acids., (Copyright © 2023. Published by Elsevier Inc.)

The sunflower Helianthus annuus L. represents the 4th largest oilseed cultivated area worldwide. Its balanced amino acid content and low content of antinutrient factors give sunflower protein a good nutritional value. However, it is underexploited as a supplement to human nutrition due to the high content of phenolic compounds that reduce the sensory quality of the product. Thus, this study aimed at obtaining a high protein and low phenolic compound sunflower flour for use in the food industry by designing separation processes with high intensity ultrasound technology. First, sunflower meal, a residue of cold-press oil extraction processing, was defatted using supercritical CO 2 technology. Subsequently, sunflower meal was subjected to different conditions for ultrasound-assisted extraction of phenolic compounds. The effects of solvent composition (water: ethanol) and pH (4 to 12) were investigated using different acoustic energies and continuous and pulsed process approaches. The employed process strategies reduced the oil content of sunflower meal by up to 90% and reduced 83% of the phenolic content. Furthermore, the protein content of sunflower flour was increased up to approximately 72% with respect to sunflower meal. The acoustic cavitation-based processes using the optimized solvent composition were efficient in breaking down the cellular structure of the plant matrix and facilitated the separation of proteins and phenolic compounds, while preserving the functional groups of the product. Therefore, a new ingredient with high protein content and potential application for human food was obtained from the residue of sunflower oil processing using green technologies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Teresa Bertoldo Pacheco reports administrative support and equipment, drugs, or supplies were provided by Institute of Food Technology. Maria Teresa Bertoldo Pacheco reports financial support was provided by State of Sao Paulo Research Foundation. Mariana Friolli reports financial support was provided by Coordination of Higher Education Personnel Improvement. Maria Teresa Bertoldo Pacheco reports a relationship with Institute of Food Technology that includes: employment. No has patent No pending to No. There are no additional relationships or activities to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The growing interest in ingredients from natural sources has expanded the need for quality assessments of plant extracts. Analytical quality-by-design (AQbD) has been increasingly applied in regulated environments such as pharmaceutical industries and, more recently, for the bioactive compounds found in botanical materials. This work aimed to obtain qualitative (overall resolution and maximum peak capacity) and quantitative performances for target analytes using AQbD principles. The analytical target profile was elaborated; critical method parameters (independent variables) that affect the critical method attributes (dependent variables) were selected from a risk assessment for a reversed-phase liquid chromatography with diode array detection (RPLC-DAD) method. YMC-Triart C18 (3.0 × 100 mm, 1.9 μm) and a gradient elution using 0.2% acetic acid and methanol:acetonitrile 1:3 (v/v) were chosen as the stationary and mobile phases, respectively. The optimal and robust conditions (temperature at 33.3 °C, flow rate of 0.68 mL.min -1 , and a gradient slope of 4.18%.min -1 ) were established by the method operable design region (MODR). The validation was performed by accuracy profiles using 90% expectation tolerance intervals for the selected compounds found in Citrus spp. using C. japonica as blank matrix. The lower limits of quantification for hesperidin, bergapten, herniarin, and citropten were 5.32, 0.40, 0.49, and 0.52 mg.L -1 , respectively (acceptance limit was set at ± 20%). Nobiletin did not show an adequate quantitative performance., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Mutations in ITM2B cause familial British, Danish, Chinese and Korean dementias. In familial British dementia (FBD) a mutation in the stop codon of the ITM2B gene (also known as BRI2 ) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer's disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons, and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. Consequently, the ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. Pathological examination of post-mortem tissue support ABri expression in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are the major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. This has implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer's disease.

Due to the complex characteristics and variable composition of apple pomace, sample preparation for chromatographic analysis is a great challenge. To solve this problem, we proposed using a solvent gradient using Pressurized Liquid Extraction (PLE), where the solvent gradually changes from water to ethanol during the extraction. Different dynamic gradients, static time, and temperatures were evaluated and showed relevant effects on the yields of target analytes. It was possible to improve extraction yields of compounds with different characteristics using the extraction solvent gradient. By coupling solid-phase extraction in-line, it was possible to separate compounds into fractions, where furfural, HMF, and chlorogenic acid gradually eluted from the adsorbent. At the same time, flavonoids were retained and eluted in the later fractions. On-line analysis by HPLC provided real-time information about the process and permitted the creation of a 3D chromatogram of the sample., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Concentrated in the skins of red grapes are the anthocyanins, the primary colorants responsible for the fruits' reddish-purple color. These colorants are recognized for their significant antioxidant properties and potent nutraceutical and pharmaceutical ingredients. Nevertheless, their widespread use is compromised by the (i) need for more efficient yet sustainable downstream processes for their recovery and (ii) by the challenges imposed by their poor stability. In this work, these drawbacks were overcome by applying eutectic solvents and stabilizing agents. Besides, the anthocyanins were successfully loaded into a solid host material (approved in both food and pharmaceutical sectors) based on silicon dioxide (SiO 2 , loading capacity: 1 extract :7 silica m/m). Summing up, with the process developed, the extraction yield (21 mg anthocyanins .g biomass -1 ) and the stability (under 55, 75, and 95 °C) of the recovered anthocyanins were over three times better than with the conventional process. Finally, the raw materials and solvents were recycled, allowing an economical and environmentally friendly downstream process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Few data exist about the efficacy of radiofrequency (RF) maze procedures in elderly patients with atrial fibrillation (AF) undergoing surgery for mitral valve disease. The aim of the present investigation was to evaluate the effects of AF ablation associated with mitral valve surgery on the recovery and long-term maintenance of sinus rhythm in elderly patients aged > 75 years. Moreover, we evaluated the effects on survival., Methods and Results: This study included 96 consecutive patients with AF (42 men and 56 women) aged > 75 years (mean age 78 ± 3) who underwent RF ablation associated with mitral valve surgery (group I). This group was compared to 209 younger patients (mean age 65 ± 8 years) treated in the same period (group II). Baseline clinical and echocardiographic characteristics were similar in the two groups. Four patients died during hospitalization, one aged > 75 years. In surviving patients at the end of the follow-up period, sinus rhythm was present respectively in 64% of the elderly and 74% of younger patients ( p = 0.778). The rate of persistence of sinus rhythm without AF recurrences (38% vs. 41%, p = 0.705) was similar in the two groups. After surgery, sinus rhythm was frequently never regained in aged patients (27% vs. 20%, p = 0.231). Elderly patients more frequently needed permanent pacing and had more hospitalizations and a higher number of non-AF atrial tachyarrhythmias. At eight-year follow-up, survival was lower in older patients (48% aged > 75 vs. 79% aged < 75 years)., Conclusion: Elderly patients had a similar long-term rate of stable sinus rhythm maintenance in comparison to younger patients after AF radiofrequency ablation associated with mitral valve surgery. However, they needed more frequent permanent pacing and had higher rates of hospitalizations and post-procedural atrial tachyarrhythmias. The effects of survival are difficult to evaluate due to the different life expectancies of the two groups.

Propolis is a bee product with a complex chemical composition formed by several species from different geographical origins. The complex propolis composition requires an accurate and reproducible characterization of samples to standardize the quality of the material sold to consumers. This work developed an ultra-high-performance liquid chromatography with a photodiode array detector method to analyze propolis phenolic compounds based on the two key propolis biomarkers, Artepillin C and p-Coumaric acid. This choice was made due to the complexity of the sample with the presence of several compounds. The optimized method was hyphenated with mass spectrometry detection allowing the detection of 23 different compounds. A step-by-step strategy was used to optimize temperature, flow rate, mobile phase composition, and re-equilibration time. Reverse-phase separation was achieved with a C18 fused-core column packed with the commercially available smallest particles (1.3 nm). Using a fused-core column with ultra-high-performance liquid chromatography allows highly efficient, sensitive, accurate, and reproducible determination of compounds extracted from propolis with an outstanding sample throughput and resolution. Optimized conditions permitted the separation of the compounds in 5.50 min with a total analysis time (sample-to-sample) of 6.50 min., (© 2022 Wiley-VCH GmbH.)

Propolis is a rich source of known and largely explored bioactive compounds with many pharmacological properties. It is used in several commercialized products, such as propolis-enriched honey, candies, mouth and throat sprays, soaps, toothpaste, and skin creams. However, the great diversity of propolis products and different types make the standardization of realistic quality control procedures challenging. Moreover, the extraction of propolis bioactive compounds depends on the technique and the solvent used. In Brazil, the Ministry of Agriculture, Livestock, and Supply (MAPA) set standards to establish commercialized propolis extracts' identity and quality. In addition, according to legislation, propolis extracts must present the main classes of phenols at 200 and 400 nm on the UV spectrum. Still, it is not specified which analysis method should be used to guarantee feasible quality control of the commercialized samples. For this, we proposed a new fast UHPLC-PDA-MS/MS method for analysis and quantification of propolis phenolic compounds. Moreover, we hypothesize that there is no efficient monitoring regarding the quality of the propolis extracts sold in Brazilian stores. Therefore, the present study aimed to perform quality control of 17 Brazilian propolis extracts produced in the Southeast region (green or brown - the most representative samples). The dry extract content (% g/mL), oxidation index (seconds), total flavonoids, and phenolics (% m/m) of each sample were compared with legislation. We conclude that using the UHPLC-PDA method and the investigation that allowed the comparison with the current legislation efficiently practical problems in the commercialization of propolis extracts. However, of the 17 analyzed samples, 6 did not meet the desired the recognized standards, denoting a lack of supervision and efficient quality control, which highlights a dangerous situation regarding the commercialization of this critical product used in several industrial fields, mainly in the food and pharmaceutical sector., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Proprioception is often impaired in poststroke individuals. This is a significant issue since altered proprioception is associated with poorer physical function outcomes poststroke. However, there is limited consensus on the best tools for assessing proprioception and support for their widespread use by clinicians. The objective is to appraise the psychometric properties of each test used to assess proprioception in poststroke individuals., Methods: A systematic search was performed according to PRISMA guidelines using the databases MEDLINE, Cochrane Library, PEDro, DiTa, and BioMedicalCentral for articles published up to January 2021., Results: Sixteen studies of low methodological quality were included. Sixteen different proprioception assessment tests were extracted. The proprioception portion of the Fugl-Meyer Assessment Scale was found to be the most valid and reliable tool for screening patients in clinical settings. Although no real gold standard exists, the technological devices demonstrated better responsiveness and measurement accuracy than clinical tests. Technological devices might be more appropriate for assessing proprioception recovery or better suited for research purposes., Discussion and Conclusions: This review revealed low-quality articles and a paucity of tests with good psychometric properties available to clinicians to properly screen and assess all subcomponents of proprioception. In perspective, technological devices, such as robotic orthoses or muscle vibration, may provide the best potential for assessing the different subcomponents of proprioception. Further studies should be conducted to develop and investigate such approaches.Video, Supplemental Digital Content 1, available at:http://links.lww.com/JNPT/A388., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

This study aimed to extract anthocyanins from dried and semi-defatted açaí pulp using green technologies based on the coupling of pressurized liquid extraction (PLE) with in-line purification through solid-phase extraction (SPE) and on-line analysis by high-performance liquid chromatography (HPLC). Critical parameters that affect the extraction efficiency and purification were investigated and optimized by response surface methodology (RSM). PLE was performed with acidified water at different pH (2.0, 4.5, and 7.0) and temperatures (40, 80, and 120 °C) at 15 MPa, 2 mL/min, and solvent-to-feed mass ratio equal to 40. SPE was optimized in a column packed with the adsorbent PoraPak™ Rxn. Different ethanol concentrations (50, 75, and 100 %) and temperatures (30, 40, and 50 °C) were evaluated for the anthocyanin's elution. The optimal conditions of the two experimental designs were determined by the RSM, firstly for PLE: 71 °C and pH 2; then using this PLE condition, the optimization of the SPE was obtained: 30 °C and 50 % ethanol. The developed PLE method provided similar anthocyanin yield to other techniques, and the coupling with SPE in-line produced an extract 5-fold more concentrated than PLE alone. Therefore, the system (PLE-SPE × HPLC-PDA) proved to be a powerful tool for monitoring the extraction process in real-time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The detection of analytes in complex organic matrices requires a series of analytical steps to obtain a reliable analysis. Sample preparation can be the most time-consuming, prolonged, and error-prone step, reducing the reliability of the investigation. This review aims to discuss the advantages and limitations of extracting bioactive compounds, sample preparation techniques, automation, and coupling with on-line detection. This review also evaluates all publications on this topic through a longitudinal bibliometric analysis, applying statistical and mathematical methods to analyze the trends, perspectives, and hot topics of this research area. Furthermore, state-of-the-art green extraction techniques for complex samples from vegetable matrices coupled with analysis systems are presented. Among the extraction techniques for liquid samples, solid-phase extraction was the most common for combined systems in the scientific literature. In contrast, for on-line extraction systems applied for solid samples, supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, and pressurized liquid extraction were the most frequent green extraction techniques.

This study aimed to describe and compare, at a national level, the measures implemented in the pediatric onco-hematology units and the number of infections among patients and healthcare staff during the first and second wave of the COVID-19 pandemic in Italy. A multicenter, descriptive, online survey was conducted between15th March and 15th April 2020 (T1) and between 1 and 31st January 2021 (T2). All the Italian Pediatric Oncology and Hematology Association (AIEOP) centers were invited to participate in the study. Data of the pre-pandemic, first, and second phase were compared. Thirty-six of the 48 AIEOP centers completed the survey (75%). Several organizational, screening, and swab measures were implemented by AIEOP centers to prevent the SARS-CoV-2 infection among patients and visitors. During the pandemic, there was a significant reduction in the number of onco-hematology inpatient beds (p < 0.001), including inpatient beds dedicated to hematopoietic stem cell transplantation (HSCT), and consultations in the outpatient clinics (p < 0.001). During the first wave, 37 pediatric patients with cancer tested positive for SARS-CoV-2 versus 174 patients during the second wave. The reduction in routine services was also greater in the second than in the first wave. All the AIEOP centers showed the capacity to adapt and promptly respond to both waves of the pandemic., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022. The Author(s).)

Background: In elderly patients with hip fracture, the prevalence of severe aortic stenosis (valve area <1 cm 2 ) is close to 5%. Few studies have evaluated the prognostic role of aortic stenosis in hip fracture surgery and none has considered the effects of the postoperative setting (intensive care unit vs general ward) on clinical outcome., Purpose: The aim of the present study was to evaluate the factors affecting mortality in patients with severe aortic stenosis undergoing surgery for hip fracture. We also evaluated whether postoperative monitoring in the intensive care unit may affect the prognosis in comparison to return to the general ward after surgery., Patients and Methods: All 2274 patients referred for hip fracture to our tertiary teaching hospital between January 1 2015 and December 31 2019 were screened for the presence of severe aortic stenosis, defined by an aortic valve area <1.0 cm 2 ., Results: The study included 66 patients (27 males, 39 females) with a mean±SD age of 85±7 years. The average time between trauma and surgery was 2.6±3 days. The mean aortic valve area was 0.74±0.15 cm 2 . Seven patients died during hospitalization (10.4%). Diabetes, having two or more comorbidities, a low degree of autonomy, heart failure, history of coronary artery disease, atrial fibrillation, postoperative delirium and pulmonary hypertension were associated with poorer outcome. In logistic multivariate analysis, the number of diseases and values of pulmonary artery pressure were the only independent factors related to mortality. In hospital mortality (12 and 9%, respectively) and complication rates were not statistically different between patients referred to the intensive care unit for postoperative monitoring and patients returned to the general ward after surgery., Conclusion: In patients undergoing hip fracture surgery, severe aortic stenosis is associated with high hospital mortality, and two or more comorbidities and pulmonary hypertension are associated with a worse prognosis. The postoperative setting (intensive care unit or general ward) does not affect outcome., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Rostagno et al.)